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J Deckert

Publications and source records attributed to J Deckert.

At least 37 records · Page 2Linked to original sources
PubMed1998

Adenosine A1 receptor and bipolar affective disorder: systematic screening of the gene and association studies.

In the present study we sought to identify genetic variation in the adenosine A1 receptor (A1AR) gene on chromosome 1q31-32.1, which through alteration of protein function or level of expression might contribute to the genetic predisposition to bipolar affective disorder. We performed a systematic mutation scan of the whole coding sequence as well as 5' and 3' untranslated regions by means of single-strand conformation analysis. The region upstream to the coding sequence we investigated contains two functional promoters. Screening 42 patients with bipolar affective disorder, we detected 11 DNA sequence variants (48T/A, 267 + 275C/T, 805T/G, 1777C/A, 1827C/T, 1904C/T, 2126G/T, 2294insT, 2776C/T, 2777del36, 2819T/G). Determining the frequency of these variants in 42 anonymous blood donors, we observed a non-significant (P < 0.06) trend towards an underrepresentation of the 2126T variant in patients when compared to controls. On the other hand, the 2777del36 and the 2819G variant were not found among the controls. These findings were followed up in a large independent replication sample. However, we were not able to confirm the initial findings in the second sample. Our data suggest that genetically determined variation of the A1AR and its two promoters do not play a major role in the development of bipolar affective disorder.

Base Sequence↗
PubMed1998

Hemicorporectomy: a case study from a physical therapy perspective.

Hemicorporectomy, literally translated, means half (hemi), body (corpus), removal (ectomy). The procedure is indicated as a last resort measure for patients with life-threatening conditions such as advanced pelvic tumors, pelvic osteomyelitis, crushing pelvic trauma, or intractable decubiti in the pelvic region. We report a case in which this mutilating procedure was performed on a 49-year-old man with extensive perineal and sacral sores. Squamous cell carcinoma was detected and isolated to the pelvic region. His medical history was significant for paraplegia secondary to a gunshot wound in 1966. The literature has documented fewer than 45 procedures of this radical nature. Few of the case studies specifically address the rehabilitation of this patient population and none of the articles researched were written from a physical therapy standpoint. Articles that addressed the concept of rehabilitation comment only that the course of rehabilitation was extensive and prolonged. This report provides an overview of the surgical procedures and specifically addresses the physical rehabilitation of this patient after his hemicorporectomy from a physical therapy perspective. This patient's physical therapy was accomplished over a time span of less than 1 month.

Amputation, Surgical↗
PubMed1998

Inhibition of [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid [AMPA] binding by the anticonvulsant valproate in clinically relevant concentrations: an autoradiographic investigation in human hippocampus.

The interaction of the anticonvulsant valproate with AMPA glutamate receptors in human post mortem hippocampus was investigated. At concentrations of > or = 100 microM valproate decreased binding of 40 nM [3H]AMPA to 45+/-56% of control level (CA 1). Clinically effective brain concentrations for valproate are estimated at 100-200 microM. Our results thus provide evidence that the anticonvulsant effects of valproate may partially be caused by interaction with AMPA receptors.

Aged↗
PubMed1998

Systematic mutation screening and association study of the A1 and A2a adenosine receptor genes in panic disorder suggest a contribution of the A2a gene to the development of disease.

Several lines of evidence suggest a contribution of adenosinergic neurotransmission to the development of panic disorder. We therefore hypothesized that variation in the A1 and A2a adenosine receptor (AR) genes modifies genetic susceptibility to panic disorder. To test this hypothesis, we screened 38 patients with panic disorder for mutations in the coding sequence of the A1AR and A2aAR genes. An association study between the identified DNA sequence variants and panic disorder was performed in an extended sample of 89 patients and matched controls. One silent mutation (716T/G) in the A1AR gene and two silent mutations (432C/T and 1083C/T) in the A2aAR gene were detected. The association sample shows a significant association between the 1083T allele (P=0.01) and 1083T/T genotype (P=0.024) of the A2AR gene and panic disorder. Our findings thus lend further support to the hypothesis that the A2aAR gene, or a locus in linkage disequilibrium with it, confers susceptibility to panic disorder. Replication studies in independent samples with nuclear families applying the transmission disequilibrium test (TDT) are warranted.

DNA Primers↗
PubMed1998

The anatomy of a hypoxic operator in Saccharomyces cerevisiae.

Aerobic repression of the hypoxic genes of Saccharomyces cerevisiae is mediated by the DNA-binding protein Rox1 and the Tup1/Ssn6 general repression complex. To determine the DNA sequence requirements for repression, we carried out a mutational analysis of the consensus Rox1-binding site and an analysis of the arrangement of the Rox1 sites into operators in the hypoxic ANB1 gene. We found that single base pair substitutions in the consensus sequence resulted in lower affinities for Rox1, and the decreased affinity of Rox1 for mutant sites correlated with the ability of these sites to repress expression of the hypoxic ANB1 gene. In addition, there was a general but not complete correlation between the strength of repression of a given hypoxic gene and the compliance of the Rox1 sites in that gene to the consensus sequence. An analysis of the ANB1 operators revealed that the two Rox1 sites within an operator acted synergistically in vivo, but that Rox1 did not bind cooperatively in vitro, suggesting the presence of a higher order repression complex in the cell. In addition, the spacing or helical phasing of the Rox1 sites was not important in repression. The differential repression by the two operators of the ANB1 gene was found to be due partly to the location of the operators and partly to the sequences between the two Rox1-binding sites in each. Finally, while Rox1 repression requires the Tup1/Ssn6 general repression complex and this complex has been proposed to require the aminoterminal regions of histones H3 and H4 for full repression of a number of genes, we found that these regions were dispensable for ANB1 repression and the repression of two other hypoxic genes.

Consensus Sequence↗
PubMed1998

Family practice residency program sites on the World Wide Web.

BACKGROUND AND OBJECTIVES: The World Wide Web is a rapidly expanding entity, and family practice residencies have begun using this technology through the development of Web sites. Our objective was to survey Web sites devoted to family practice residencies. METHODS: We sent a national survey to 451 family practice residency directors. RESULTS: Of 241 returned surveys, 113 residencies reported an existing Web site. Seventy-four percent of Web sites were created by faculty, but 31% also involved residents in creation. Resident recruitment was the most successful goal of Web sites; 42% of programs reported "moderate" to "very successful" results. However, most programs reported that it was too early to evaluate the goals listed in the survey. CONCLUSIONS: Family practice residencies have an increasingly significant presence on the Web. The development, content, and goals of the sites are similar across programs regardless of creation date, but the evaluation of the success of these goals is at an early stage for most programs.

Computer Communication Networks↗
PubMed1997

Neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) and panic disorder: an association study.

Anxiety disorders have been reported to be associated with low-voltage EEG (LVEEG). Some cases with LVEEG (approximately 1/3) have been linked to chromosome 20q13.2q13.3. In the same chromosomal region, the gene for the neuronal nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4) has been located. We therefore tested the hypothesis that polymorphisms in the CHRNA4 gene show an allelic association with panic disorder. We examined the allele frequencies of three different CHRNA4 polymorphisms in patients with panic disorder and in healthy controls. No significant differences in the allele frequencies of these three polymorphisms were noted. This study does not support an association between panic disorder and the CHRNA4 gene.

Adult↗
PubMed1997

Approaches to the study of Rox1 repression of the hypoxic genes in the yeast Saccharomyces cerevisiae.

The yeast Saccharomyces cerevisiae is a facultative aerobe that responds to changes in oxygen tension by changing patterns of gene expression. One set of genes that responds to this environmental cue is the hypoxic genes. Oxygen levels are sensed by changes in heme biosynthesis, which controls the transcription of the ROX1 gene, encoding a protein that binds to the regulatory region of each hypoxic gene to repress transcription. Several experimental molecular and genetic approaches are described here to study Rox1 repression. Derepression of the hypoxic genes is rapid, and one model for such a response requires that Rox1 have a short half-life. This was demonstrated to be the case by immunoblotting using a c-myc epitope-tagged protein. Rox1 repression is mediated through the general repressors Ssn6 and Tup1. To explore possible interactions among these proteins, all three were expressed and partially purified using a baculovirus expression system and histidine-tagged proteins. The effect of Ssn6 and Tup1 on the formation of Rox1-DNA complexes was explored using these purified proteins by both electrophoretic mobility shift and DNase I protection assays. We found that Rox1 DNA-binding activity decayed rapidly and that Ssn6 could stabilize and restore lost activity. Finally, genetic selections are described for the isolation of loss-of-function mutations in Rox1. Also, schemes are proposed for the reversion of such mutations. These selections have been extended to genetic analyses of the TUP1 and SSN6 genes.

DNA, Fungal↗
PubMed1997

Mapping of the human adenosine A2a receptor gene: relationship to potential schizophrenia loci on chromosome 22q and exclusion from the CATCH 22 region.

Chromosome 22 contains two potential schizophrenia loci on chromosomal regions 22q11.2 and 22q12-13. In the present study we report results from linkage mapping of the gene coding for the human A2a adenosine receptor (AR), which is one of two receptors mediating central nervous system effects of adenosine. From seven CEPH (Centre d'Etude du Polymorphisme Humain) families, 120 individuals were typed utilizing an intragenic restriction fragment length polymorphism. Significant linkage was found with many markers on chromosome 22. A 10-cM 1000:1 support interval between markers D22S301 and D22S300 is defined on the CHLC (Cooperative Human Linkage Center) framework map of chromosome 22. Localization of the A2aAR gene outside the CATCH 22 syndrome region on 22q11.2 is demonstrated by the observation of heterozygous individuals with defined 2-Mb deletions from this region. Thus, the A2aAR gene is not the schizophrenia susceptibility gene suspected in the CATCH 22 syndrome region on 22q11.2, but remains a candidate for a schizophrenia susceptibility gene on 22q12-13.

Abnormalities, Multiple↗
PubMed1997

Regulation of hypoxic gene expression in yeast.

Baker's yeast, Saccharomyces cerevisiae, can adapt to growth under severe oxygen limitation. Two regulatory systems are described here that control this adaptation. The first involves a heme-dependent repression mechanism. Cells sense hypoxia through the inability to maintain oxygen-dependent heme biosynthesis. Under aerobic conditions, heme accumulates and serves as an effector for the transcriptional activator Hap1. The heme-Hap1 complex activates transcription of the ROX1 gene that encodes a repressor of one set of hypoxic genes. Under hypoxic conditions, heme levels fall, and a heme-deficient Hap1 complex represses ROX1 expression. As a consequence, the hypoxic genes are derepressed. The second regulatory system activates gene expression in response to a variety of stress conditions, including oxygen limitation. Oxygen sensing in this system is heme-independent. The same DNA sequence mediates transcriptional activation of each stress signal.

Base Sequence↗
PubMed1997

Functional promoter polymorphism of the human serotonin transporter: lack of association with panic disorder.

To probe the hypothesis of a role for a functionally relevant 44 bp insertion/deletion of the serotonin transporter promoter in the aetiopathogenesis of panic disorder, we determined the allele frequency of the variant in two samples (combined n = 158) of panic disorder patients (DSMIII-R) and compared it with its allele frequency in two ethnically matched control samples (combined n = 169). The fact that no difference could be observed (x 2 analysis) argues against a major role for this serotonin transporter promoter polymorphism in the aetiopathogenesis of panic disorder.

Alleles↗
PubMed1997

Isolation and classification of a family of cyclin gene homologues in Lupinus luteus.

The lupine (Lupinus luteus cv. Ventus) cDNA clones encoding homologues of cyclin (CycB1;2, CycB1;3, CycB1;4) have been isolated from cDNA library prepared from roots inoculated with Bradyrhizobium lupini. Comparison of the deduced amino-acid sequences of CycB1;2, CycB1;3, CycB1;4 and previously described CycB1;1 (Deckert et al. 1996, Biochimie 78, 90-94) showed that they share 46-65% of identical amino acids. The presence of conserved residues (Renaudin et. al., in The Plant Cell Cycle, in the press; Renaudin et al., Plant Mol. Biol, in the press) along with phylogenetic analysis of known plant cyclins revealed that the four lupine sequences belong to subgroup 1 of B-like mitotic cyclins.

Amino Acid Sequence↗
PubMed1996

Human adenosine A2a receptor (A2aAR) gene: systematic mutation screening in patients with schizophrenia.

Several lines of evidence suggest an involvement of adenosine A2a receptor (A2aAR) mediated adenosinergic neuromodulation in the etiopathogenesis of schizophrenia. We therefore performed a systematic mutation scan of the complete coding region of the human A2aAR gene in a sample of 42 schizophrenic patients. We detected one rare naturally occurring receptor variant (Gly-340-Ser) and two silent mutations (405C/T and 1083C/T). To our knowledge the Gly-340-Ser substitution is the first naturally occurring molecular variant of the A2aAR identified. Determining the frequency of the three variants in 42 unrelated healthy controls, we observed a significant trend towards an overrepresentation of the 1083T variant in patients when compared to controls (p = 0.041). This trend was followed up in a large independent replication sample. However, we were not able to confirm the original trend in the second sample (p = 0.367). The Ser-340 variant was found in a single schizophrenic individual. Investigation of the patient's family revealed independent segregation between the Ser-340 variant and psychiatric illness. Our data suggest that genetically determined structural variation of the A2aAR does not play a major role in the development of schizophrenia.

Alleles↗
PubMed1996

The isolation of lupine cDNA clone coding for putative cyclin protein.

The complex of p34cdc2 protein kinase and cyclin is a key regulator of eukaryotic cell division and has been mostly investigated in yeast and animals. We have isolated a cDNA clone corresponding to cyclin from yellow lupine (Lupinus luteus). The cDNA clone CycBla-ll is 1692 bp in length and encodes a protein of predicted molecular mass 48.7 kDa. The lupine cyclin-like clone contains two domains: destruction and cyclin box, responsible for the function during the cell cycle. The amino acid comparison of CycBla-ll with conserved regions of other cyclins indicates that the lupine cDNA sequence represents mitotic cyclin of type B.

Amino Acid Sequence↗
PubMed1996

Adverse CNS-effects of beta-adrenoceptor blockers.

In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

Adrenergic beta-Antagonists↗
PubMed1995

Human adenosine A1 receptor gene: systematic screening for DNA sequence variation and linkage mapping on chromosome 1q31-32.1 using a silent polymorphism in the coding region.

Adenosine is a major inhibitory neuromodulator in the central nervous system. One of the receptors mediating the central effects of adenosine is the adenosine A1 receptor. We performed a systematic mutation scan of the coding region of the adenosine A1 receptor gene to explore its variability in the general population. Investigating 40 unrelated healthy subjects by single-strand conformation analysis no sequence changes of likely functional relevance were observed. We detected, however, a frequent T to G substitution at nucleotide position 716 which constitutes the first variant described in an adenosine receptor gene. It was used for fine scale linkage mapping of the A1 gene. Employing a polymerase-chain-reaction-based restriction assay, we genotyped 7 CEPH families (Centre d'Etude du Polymorphisme Humaine) and mapped the receptor in a gene cluster around the renin gene on chromosome 1q31-32.1. In addition, we utilized the 716T/G polymorphism to demonstrate biallelic expression of the adenosine A1 receptor gene in adult human brain.

Adult↗
PubMed1995

Regional differences in the interaction of the excitotoxins domoate and L-beta-oxalyl-amino-alanine with [3H]kainate binding sites in human hippocampus.

The excitotoxic amino acid domoate causes anterograde amnesia and memory deficits while the excitotoxin L-beta-oxalyl-amino-alanine (L-BOAA) is considered the causative agent of the motoneurone disorder, neurolathyrism. Employing quantitative autoradiography we investigated the potency of domoate and L-BOAA to inhibit [3H]kainate binding in human hippocampus. Domoate inhibited binding of [3H]kainate with inhibition constants between 5.8 +/- 2.8 nM (deep layers of gyrus parahippocampalis) and 200.9 +/- 247.8 nM (CA1 region of hippocampus). It was about a thousandfold more potent than L-BOAA with inhibition constants between 2.1 +/- 0.5 microM (superficial layers of gyrus parahippocampalis) and 51.0 +/- 41.9 microM (CA2/3 region of hippocampus). Interestingly, L-BOAA showed lowest affinity to [3H]kainate binding sites in those regions in which domoate showed highest affinity (e.g. CA2/3) and vice versa (e.g. CA1). These data further support the notion that the neurological symptoms observed after domoate intoxication are due to an excitotoxic action at kainate receptors and provide evidence for heterogeneity of kainate receptors in human hippocampus.

Aged↗